Anti-inflammatory effects of indomethacin's methyl ester derivative and induction of apoptosis in HL-60 cells

Su Hui Chao, An-Bang Wu, Chia Jung Lee, Fu An Chen, Ching Chiung Wang

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Abstract

Indomethacin is used as an anti-inflammatory drug and a nonselective cyclooxygenase inhibitor. When indomethacin in methanol was photo-irradiated with an Hg lamp, methyl ester, ethyl ester, and γ-lactone derivatives of indomethacin were produced. In the present study, we found that the methyl ester derivative of indomethacin (M-IN) could more potently inhibit prostaglandin E2 (PGE2) and nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX 2) protein expression from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells than indomethacin, similar to the effect of a non-steroidal anti-inflammatory drugs (NSAID). On the other hand, the results showed that M-IN with an IC50 value maintained at 36.9 μg/ml for 12 h exhibited stronger cytotoxicity than ethyl ester, γ-lactone derivatives of indomethacin, and indomethacin in promyelocytic leukemia HL-60 cells. Moreover, a series of biochemical analyses determined that M-IN caused apoptotic bodies, DNA fragmentation, and enhanced PARP and pro-caspase 3 degradation in HL-60 cells. These above results indicate that the photosynthesized product, M-IN, had stronger anti-inflammatory effects in LPS-stimulated RAW 264.7 cells and cytotoxicity effects in HL-60 cells than the parent drug, indomethacin.

Original languageEnglish
Pages (from-to)2206-2210
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume28
Issue number12
Publication statusPublished - Dec 2005

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Keywords

  • [1-(4-chloro-benzoyl)-5-methoxy-2-methyl-indol-3-yl]-acetic acid methyl ester
  • Anti-inflammatory drug
  • Apoptosis
  • Caspase 3
  • Cyclooxygenase

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

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